1. Field of the Invention
This invention relates to a method for greatly accelerating the rate of delivery of codeine, and derivatives thereof, to the central nervous system by administration via the nasal route to provide extremely rapid response in the prevention or treatment of pain or relief of cough in a patient in need of such prevention or treatment. This invention relates to a method for greatly accelerating the rate of delivery of codeine, and derivatives thereof, to the central nervous system by administration via the nasal route to provide extremely rapid response in the prevention or treatment of cough in a patient in need of such prevention or treatment. This method also provides for direct absorption of codeine into the central nervous system, bypassing the metabolic enzymes circulating in the bloodstream that would otherwise destroy codeine administered by another route.
2. Description of the Related Art
Opioid analgesics are the most potent pain-relieving drugs currently available. Furthermore, of all analgesics, they have the broadest range of efficacy, providing the most reliable method for rapidly relieving pain. However, side effects, including respiratory depression, are common.
Opioids produce analgesia by actions in the central nervous system. They activate pain-inhibitory neurons and directly inhibit pain-transmission neurons. Most of the commercially available opioid analgesics act at the same opiate receptor (the xcexcreceptor), differing mainly in potency, speed of onset, duration of action, and optimal route of administration.
Opioid compounds also have antitussive (i.e., cough-suppressant) effects, via their direction action on the neural cough-control center in the medulla. Cough suppression often occurs with lower doses than those needed for analgesia. For example, an oral dose of 30 to 60 mg of codeine is typically required to produce analgesia. However, a 10- or 20-mg oral dose of codeine, although ineffective for analgesia, produces a demonstrable antitussive effect. Higher doses of codeine produce even more suppression of chronic cough.
The most rapid relief with opioids is obtained by IV administration; relief with oral administration is significantly slower. Common side effects include nausea, vomiting, sedation, and constipation. These effects are dose-related, and there is great variability among patients in the doses that relieve pain and produce side effects. Because of this, initiation of therapy requires titration to optimal dose and interval.
Codeine (methyl morphine) is an opioid compound chemically closely related to morphine, but with only one-twentieth of the narcotic action, and one-third the antitussive activity, of morphine. In contrast to morphine, codeine is approximately 60% as effective orally as parenterally, both as an analgesic and as a respiratory depressant. Very few opioids have so high an oral-parenteral potency ratio. The greater oral efficacy of codeine is due to less first-pass metabolism in the liver. Once absorbed, codeine is metabolized by the liver and excreted chiefly in the urine, largely in inactive forms. A small fraction (approximately 10%) of administered codeine is demethylated to form morphine, and both free and conjugated morphine can be found in the urine after therapeutic doses of codeine. Codeine has an exceptionally low affinity for opioid receptors, and much of the analgesic effect of orally-administered codeine is likely due to its conversion to morphine. However, its antitussive actions probably involve distinct receptors that bind codeine itself. The half-life of codeine in plasma is 2 to 4 hours.
A major object of the present invention is to provide a method for safely and conveniently administering codeine to a patient in need of treatment of pain, in order to produce a rapid and reliable response in less time than current dosage forms. The method comprises the intranasal administration of an effective amount of codeine to a patient suffering from pain.
A further object of the present invention is to provide a method for safely and conveniently administering codeine to a patient in need of treatment of cough, in order to produce a rapid and reliable response in less time than current dosage forms. The method comprises the intranasal administration of an effective amount of codeine to a patient suffering from uncontrolled cough.
The objective of the present invention is to improve the rate of delivery of codeine to the central nervous system by administering codeine via the nasal route in order to speed the onset of effect and reduce the dose required for its beneficial effect. Intranasal delivery will improve drug bioavailability by direct absorption into the central nervous system, thereby avoiding extensive first-pass metabolism which may significantly lower the plasma concentrations of codeine when it is administered via another route. Also, intranasal delivery will produce less constipation than the oral route. As a result, small doses of codeine, or derivatives thereof, can be administered which will result in fewer side effects, and the drug will be more tolerable and more effective in patients suffering from pain or cough. Importantly, since codeine is rapidly effective following intranasal administration, establishment of an ideal dose for a particular patient is greatly facilitated.
Intranasal dosage forms containing codeine in combination with other drugs used in the treatment of pain and/or chronic cough may also be employed in the practice of the present invention. Such additional drugs include, but are not limited to, opioid and/or nonopioid analgesics, and opioid and/or nonopioid antitussives.
With the foregoing and other objects, advantages and features of the invention that will become hereinafter apparent, the nature of the invention is further explained in the following detailed description of the preferred embodiments of the invention and in the appended claims.